检索结果-内蒙古大学图书馆

第11届世界华人药物化学研讨会（ISCMC 2018）

作者： Weishuo Fang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College

The pentacyclic triterpene oleanolic acid(OA) with known famesoid X receptor(FXR)modulatory activity was modified at A-ring(C-3) and C-ring(C-12) positions to find new FXR-interacting *** agonist-and antagonist-based ligand-FXR binding models were established to assist the design of structural modifications at both sites on A-and *** potent antagonists were found,in addition to a few weak to moderate agonists and compounds with coactivation effects with CDCA,the internal FXR agonist in luciferase-based cell *** vivo PD and PK assessment are in progress.

关键词： farnesoid X receptor FXR triterpene oleanolic acid

来源：评论

学校读者我要写书评

暂无评论

Strategic Design of Catalytic Lysine-Targeting Reversible Covalent BCR-ABL Inhibitors**

引用

Angewandte Chemie 2021年第31期133卷

作者： Dr. David Quach Dr. Guanghui Tang Dr. Jothi Anantharajan Dr. Nithya Baburajendran Dr. Anders Poulsen John L. K. Wee Priya Retna Rong Li Boping Liu Doris H. Y. Tee Perlyn Z. Kwek Dr. Joma K. Joy Wan-Qi Yang Dr. Chong-Jing Zhang Dr. Klement Foo Dr. Thomas H. Keller Prof. Dr. Shao Q. Yao NUS Graduate School for Integrative Sciences and Engineering 21 Lower Kent Ridge University Hall Tan China Tuan Wing #04-02 Singapore 119077 Singapore Experimental Drug Development Centre 10 Biopolis Road Chromos #05-01 Singapore 138670 Singapore Department of Chemistry National University of Singapore Singapore 117543 Singapore State Key Laboratory of Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100050 China

来源：评论

学校读者我要写书评

暂无评论

Potassium 2-(l-hydroxypentyl)-benzoate attenuates neuroinflammatory responses and upregulates heme oxygenase-1 in systemic lipopolysaccharide-induced inflammation in mice

引用

Acta Pharmaceutica Sinica B 2017年第4期7卷 470-478页

作者： Chunyang Zhao Weizhen Hou Hui Lei Longjian Huang Shan Wang Dandan Cui Changhong Xing Xiaoliang Wang Ying Peng State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College Departments of Radiology and Neurology Massachusetts General Hospital Harvard Medical School

A neuroinflammatory response is commonly involved in the progression of many neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate(PHPB), a novel neuroprotective compound, has shown promising effects in the treatment of ischemic stroke and Alzheimer's disease(AD). In the present study, the anti-inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6 mice administered a single intraperitoneal(i.p.) injection of lipopolysaccharide(LPS). Levels of i NOS and the cytokines TNFα, IL-1β and IL-10 were elevated in plasma, cerebral cortex and hippocampus after LPS injection and the number of microglia and astrocytes in cortex and hippocampus were increased. LPS also upregulated the expression of heme oxygenase-1(HO-1) in the cortex and hippocampus. PHPB reduced the levels of i NOS and cytokines in the plasma and brain, decreased the number of microglia and astrocytes and further enhanced the upregulation of HO-1. In addition, PHPB inhibited the LPS-induced phosphorylation of ERK, P38 and JNK. These results suggest that PHPB is a potential candidate in the treatment of neurodegenerative diseases through inhibiting neuroinflammation.

关键词： PHPB Neuroinflammation LPS MAPK Heme oxygenase-1

来源：评论

学校读者我要写书评

暂无评论

Development of an XBP1 agonist,HLJ2,as a potential therapeutic agent for ulcerative colitis

引用

中国药理学与毒理学杂志 2017年第10期31卷 970-971页

作者： Xiao-nan TANG Hai-jing ZHANG Guang-ming SONG Hua-chen SONG Wen-jie WANG Lian-qiu WU State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel *** and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decreased weight loss,colon contracture,disease activity index(DAI),colon mucosa damage index(CMDI)and histopathological index(HI).HLJ2 also decreased myeloperoxidase(MPO)activity and reduced production of the inflammatory cytokines TNF-α,IL^(-1)β,and ***2 improved intestinal mucosa damage induced by dextran sodium sulfate(DSS)and increased the expression of ZO-1 and *** 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2,including increased abundance of probiotics such as Lachnospiraceae,Prevotellaceae,and *** the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae,Porphyromonadaceae,Deferribacteraceae,and Pseudomonadaceae in HLJ2-treated mice compared with untreated *** Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation,regulates the intestinal flora,and protects the intestinal *** is thus a potential therapeutic agent for ulcerative colitis.

关键词： ulcerative colitis XBP1 intestinal flora intestinal mucosa cytokines

来源：评论

学校读者我要写书评

暂无评论

Antidepressant-Like Effects of Ginseng and Ginsenosides in Central Nervous System

引用

神经药理学报 2018年第6期 27-28页

作者： ZENG Ting WANG Zhen-zhen CHEN Nai-hong College of Pharmacy Hunan University of Chinese Medicine State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical College

Depression is a devastating mental disorder and major depressive disorder afflicts 16% of the global population in their lives. Currently available classical antidepressants require a minimum of 2～4 weeks of continuous treatment to elicit therapeutic relief in depressed patients and are associated with high rates of non-responsiveness and various side effects. Therefore,more safe and effective antidepressant therapies are needed. Here,we review recent advances in understanding the molecular mechanisms underlying the efficacy of traditional chinese medicine-ginseng and ginsenosides in ameliorating the symptoms of depression in humans and animal models. For instance,Panax ginseng exhibited an antidepressant-like effect through the BDNF/TrkB and Sirt 1/NF-κB signaling pathways. The anti-depression efficacy of ginseng total saponins may be largely attributable to its peripheral anti-inflammatory activity,interfering with hippocampal GSK-3β-CREB signaling pathway,reversing decrease of some plasticity-related proteins,and modulating 5-HT and 5-HT2 AR expressions after depression. P. ginseng extract exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant( nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the HPA axis mechanism. Wild ginseng extract and intestinal metabolite of ginseng,20(S)-protopanaxadiol modulates depression-like behavior by regulating the expression of hypothalamic corticotrophin-releasing factor,Neuropeptide Y,glucocorticoid receptor,BDNF and neurofilament-L in hippocampus. Ginsenoside Rg1 displayed antidepressant activity through alleviating CORT-induced gap junction dysfunction,modulating the HPA and the HPG axis,activating the BDNF signaling pathway,upregulating hippocampal neurogenesis,and increasing protein kinase A( PKA) and cAMP-CREB phosphorylation levels. Ginsenoside Rg3 exerted antidepressant effect by regulating noradrenaline,adrenocorticotropic horm

关键词： Antidepressant-Like Effects of Ginseng and Ginsenosides in Central Nervous System

来源：评论

学校读者我要写书评

暂无评论

NLRP3 Inflammasome Activation in the Thymus of MPTP-Induced Parkinsonian Mouse Model

引用

神经药理学报 2018年第6期 25-26页

作者： WEN Lu WANG Shuo YUAN Yu-he State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica&Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical College College of Pharmacy Hunan University of Chinese Medicine

Purpose:Ample evidence shows that Parkinson's disease( PD) is more than simply a central nervous system( CNS) disorder:the immune system appears to participate in PD pathogenesis. Extracellular misfolded α-synuclein( α-syn) may trigger an inflammatory response in the brain. Abnormal immune responses are involved in the development of PD,but little is known about the relationship between the thymus malfunction and the pathogenesis of PD. The present study investigated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine( MPTP)-induced impairment in thymus and explored possible mechanisms involved in PD pathogenesis. Methods:After subcutaneous injection of MPTP( 25 mg·kg-1) every 4 days for 40-days. Mice were anesthetized with chloral( 400 mg·kg-1,i.p.). The thymus gland was rapidly dissectedstored at-80℃ for biochemical analysis. In addition,mice were perfused with 4% paraformaldehyde( PFA) dissolved in PBS. After perfusion,tissues were collected for histological analysis,including histopathology and immunohistochemistry( IHC),transmission electron microscopy( TEM),western blotting(WB) and enzyme-linked immunosorbent assay( ELISA). Reuslts:After subcutaneous injection of MPTP( 25 mg·kg-1) every 4 days for 40-days,immune responses became unbalanced,with increased IL-1β concentrations. On histopathology,mice treated with MPTP displayed pathological involution and damaged ultrastructure of the thymus. Both the PD-related oligomeric α-synuclein and oxidative stress related nitrated-α-synuclein( Tyr125,Tyr133) in mice treated with MPTP were elevated. Correspondingly,oxidative stress damage was detected in the form of increased 8-hydroxyguanosine staining. Moreover,MPTP significantly increased expression of caspase-8,NF-κB,NLPR3,and caspase-1 in the thymus. Discussion:These results suggested that MPTP was toxic to mouse thymus via a mechanism involving the NF-κB and NLRP3 inflammasome pathway. These results suggested that environmental factors may lead to pathological changes in t

关键词： NLRP3 Inflammasome Activation in the Thymus of MPTP-Induced Parkinsonian Mouse Model Model

来源：评论

学校读者我要写书评

暂无评论

Hsp90β inhibitors prevent GLT-1 degradation but have no beneficial efficacy on absence epilepsy

引用

中国药理学与毒理学杂志 2018年第9期32卷 724-724页

作者： PENG Yu-chen WANG Shan ZHANG Yong HUANG Long-jian ZHOU Yu-jun WANG Xiao-liang PENG Ying State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China

OBJECTIVE To examine whether17 AAG and STA9090 have anticonvulsant activity in absence *** For the acute seizure study,each group of mice received VPA(dissolved in saline) 100 mg·kg-1,17 AAG(dissolved in 50 μL DMSO) 25 mg·kg-1 or STA9090(dissolved in 20 μL DMSO) 50 mg·kg-1 by oral gavage *** control group received DMSO *** minutes after oral gavage,PTZ 80 mg·kg-1 was intraperitoneal injected to induce acute *** number of seizures refers to the total number of epileptic mice after PTZ *** latency was defined by the time elapsed from PTZ injection to the occurrence of the first *** levels of Hsp90β,GLT-1,GFAP and 20 S proteasome β1 in the cortex and hippocampus were detected by Western *** The mortality were60% for 17 AAG and 43% for STA9090,and the mortality of valproate group dropped to 20%which decreased by 33.3% compared to model *** latency of valproate group obviously prolonged compared to model group(P<0.05).But the results demonstrated that 17 AAG and STA9090 had no significant differences in seizure *** result of Western blotting has shown that inhibition of Hsp90β significantly reduced expressions of both membrane and cytosolic Hsp90β in the hippocampus and cortex of each group of ***,the expressions of GLT-1 and GFAP did not show the significant difference in the cortex and *** expression of 20 S proteasome β1 had not been obviously changed in the cortex and hippocampus among the *** 17 AAG and STA9090 did not have anticonvulsant activity and did not increase the stability of GLT-1 by disrupting proteasome-dependent GLT-1 degradation in PTZ induced mice of absence epilepsy.

关键词： Hsp90β inhibitor epilepsy GLT-1 absence epilepsy

来源：评论

学校读者我要写书评

暂无评论

Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-R in vitro and in diabetic KKAy mice

引用

Acta Pharmaceutica Sinica B 2017年第4期7卷 461-469页

作者： Quan Liu Shuainan Liu Lihui Gao Sujuan Sun Yi Huan Caina Li Yue Wang Nan Guo Zhufang Shen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Biomedical Engineering Research Center Kunming Medical UniversityKunming 650500China

Refined-JQ(JQ-R) is a mixture of refined extracts from Coptis chinensis(Ranunculaceae),Astragalus membranaceus(Leguminosae) and Lonicera japonica(Caprifoliaceae), the three major herbs of Jin Qi-Jiang Tang tablet, a traditional Chinese medicine(TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KK^(Ay)mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid(PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KK^(Ay)mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase(SOD) and decreased malondialdehyde(MDA) as well as inducible nitric oxide synthase(iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B(NF-κB p65), inhibitor of NF-κB(IκBα), c-Jun N-terminal kinase(JNK1/2) and extracellular-signal-regulated kinases(ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KK^(Ay)mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.

关键词： TCM Type 2 diabetes mellitus Insulin signalling Inflammation Oxidative stress

来源：评论

学校读者我要写书评

暂无评论

Novel chlorine-containing curcumin analogue CAK06 promotes neuroprotection and rapid antidepressant through Nrf2-induced anti-inflammatory and antioxidant effects

引用

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2025年 e00600页

作者： Tao Chen Suyu Yin Ruxu Yue Chao Pi Ying Zuo Yongqiang Jiang Wenwu Zheng Jun Jiang Yan Yang Shifeng Chu Kezhi Liu Yumeng Wei Ling Zhao Key Laboratory of Medical Electrophysiology Ministry of Education School of Pharmacy Southwest Medical University Luzhou 646000 PR China Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing The Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou Sichuan 646000 PR China Central Nervous System Drug Key Laboratory of Sichuan Province School of Pharmacy Southwest Medical University Luzhou Sichuan 646000 PR China Department of Psychiatry Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou The Affiliated Hospital Southwest Medical University Luzhou Sichuan 646000 PR China Pharmacy Department Chongqing Emergency Medical Center Chongqing University Central Hospital Chongqing 400014 China. Department of Psychiatry Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou The Affiliated Hospital Southwest Medical University Luzhou Sichuan 646000 PR China. Department of Comprehensive Medicine The Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou Sichuan 646000 PR China. Department of Cardiology The Affiliated Hospital of Southwest Medical University Luzhou Sichuan 646000 China. Department of Thyroid Surgery The Affiliated Hospital Southwest Medical University Luzhou Sichuan 646000 PR China. Key Laboratory of Medical Electrophysiology Ministry of Education School of Pharmacy Southwest Medical University Luzhou 646000 PR China. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China. Department of Psychiatry Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou The Affiliated Hospital Southwest Medical University Luzhou Sichuan 646000 PR China. Electronic address: kingzliu@163.com. Central Nervous

Currently, conventional antidepressants are often limited by poor efficacy and delayed onset, and there is an urgent need for the development of rapid acting antidepressant alternatives. The aim of this study was to develop novel antidepressants with a rapid onset of action by inhibiting inflammation and oxidative stress. A series of chlorine-containing curcumin analogues were designed and synthesized. Among them, compound CAK06 exhibited the highest potency and most robust antidepressant activity, as demonstrated through ABTS free radical ion scavenging assays, relative proliferation rate measurements, and both hydrogen peroxide and corticosterone injury models. In the lipopolysaccharide-induced BV2 cell stress model, treatment with CAK06 resulted in a 69 % decrease in nitric oxide levels and a 52 % reduction in the fluorescence intensity of reactive oxygen species compared to the model group. qRT-PCR results showed that CAK06 upregulated the expression of anti-inflammatory and antioxidant genes while downregulating the expression of pro-inflammatory genes. In the CUMS depression model, CAK06 exerted rapid antidepressant effects after 14 days of oral administration. Notably, after 28 days, CAK06 produced a more pronounced improvement in depression-like behaviors compared to the widely used antidepressant fluoxetine. Mechanistically, molecular docking, Western blot, and Elisa results indicated that CAK06 may alleviate oxidative stress, inflammatory responses, and enhance synaptic plasticity in CUMS mice via the Nrf2-HO-1/BDNF-TrkB pathway. These results suggest that the new compound CAK06 exhibits rapid antidepressant effects, positioning it as a promising novel antidepressant candidate.

关键词： Curcumin analogues Depression Neuroprotection Oxidative stress

来源：评论

学校读者我要写书评

暂无评论

Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease

引用

中国药理学报（英文版） 2017年第10期38卷 1317-1328页

作者： Qiu-shuang ZHANG Yang HENG Zheng MOU Ju-yang HUANG Yu-he YUAN Nai-hong CHEN State Key Laboratory of Bioaotive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China State Key Laboratory of Bioaotive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China College of Pharmacy Hunan University of Chinese Medicine Changsha 410208 China

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model remains the most commonly used animal model of Parkinson's disease (PD).There are three MPTP-treatment schemes:acute,subacute and *** the advantages of the period and similarity to PD,the subacute model was often chosen to assess the validity of new candidates,but the changes caused by the subacute MPTP treatment and the appropriate positive control for this model remain to be further *** aim of this study was:to estimate the value of the subacute MPTP mouse model in aspects of behavioral performance,biochemical changes and pathological abnormalities,and to find effective positive *** C57BL/6 mice were injected with MPTP (30 mg·kg-1-d-1,ip) for 5 consecutive *** days before MPTP injection,the mice were orally administered selegiline (3 mg-kg1-d-1),pramipexole (3 mg·kg-1-d-1),or medopar (100 mg·kg-1-d-1) for 18 *** performance was assessed in the open field test,pole test and rotarod *** in the striatum were detected using *** levels were measured by Western *** characteristics were examined by *** changes were observed by electron *** subacute MPTP treatment did not induce evident motor defects despite severe injuries in the dopaminergic ***,MPTP significantly increased the α-synuclein levels and the number of astrocytes in the striatum,and destroyed the blood-brain barrier (BBB) in the substantia nigra pars *** selegiline and pramipexole were able to protect the mice against MPTP *** conclude that the subacute MPTP mouse model does not show visible motor defects;it is not enough to evaluate the validity of a candidate just based on behavioral examination,much attention should also be paid to the alterations in neurotransmitters,astrocytes,α-synuclein and the *** addition,selegiline or pramipexole is a better choice than medopar as

关键词： Parkinson's disease MPTP model selegiline pramipexole medopar behavioral compensation astrocytes α-synuclein blood brain barrier myelin sheath

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：